Analgesics are widely used in the treatment of mild pain due to CNS disorders and of more severe pain due to diseases such as cancer. Many of the agents commonly used to relieve instances of severe pain are extremely dangerous due to their potency and to their addicting properties. Morphine is among such analgesic agents, and causes severe physical dependence. Even with such drawback, morphine is extensively used simply because of the non-existence of a more desirable agent. A great deal of research has been devoted, however, to finding compounds capable of alleviating severe pain to the degree accomplished with morphine, but which display little or no physical dependence capacity. Among the more recent discoveries is the series of compounds referred to generally as the "phenylmorphans." May and Murphy reported that racemic 5-(3-hydroxyphenyl)-2-methylmorphan possesses an analgesic potency nearly equivalent to that of morphine, J. Org. Chem., 20, 1197 (1955). May and Takeda later reported that the (-)-isomer of 5-(3-hydroxyphenyl)-2-methylmorphan is an analgesic with morphine-like potency but with no physical dependence capacity, J. Med. Chem., 13, 805 (1970).
One of the major difficulties with the early syntheses of this extremely potent series of compounds was the low overall yields and the difficulty in handling the intermediates. Rogers and May recently reported an improved synthesis of (-)-5-(3-hydroxyphenyl)-2-methylmorphan, but still the overall yield was only one percent, J. Med. Chem., 17, 1328 (1974). A number of novel 5-(3-hydroxyphenyl)-2-(substituted)morphans have been prepared and evaluated by Ong and co-workers, J. Med. Chem., 17, 133 (1974). None, however, were as potent as the 5-(3-hydroxyphenyl)-2-methylmorphan.
To date, no phenylmorphans having various substituents at positions other than the morphan 2-position have been prepared. An object of this invention is to provide certain 5-phenylmorphans having alkyl and alkenyl substituents at the 3 and 7-positions. Another object of the invention is to provide an improved synthesis of both new and known phenylmorphans.